Effect of Rimantadine Treatment on Clinical Manifestations and Otologic Complications in Adults Experimentally Infected with Influenza A (H1N1) Virus

Abstract

Susceptible adults (n Å 105) were enrolled into a randomized double-blind study of rimantadine treatment of experimental influenza A infection. Subjects were cloistered for 8 days and challenged with a rimantadine-sensitive strain of influenza A H1N1 virus at the end of the first day. Fortyeight hours after challenge and for 8 days, 54 subjects received placebo and 51 received rimantadine (100 mg orally, twice a day). Symptoms, signs, and pathophysiologies were monitored. Nine subjects were not infected. Seventeen subjects (38%) in the rimantadine and 26 (53%) in the placebo group became ill. A beneficial effect of rimantadine was documented for virus shedding, symptom load, and sinus pain. Rimantadine had no effect on nasal patency, mucociliary clearance, nasal signs, or on symptoms and signs of otologic complications. These results do not support a preventive effect of rimantadine on the development of otologic manifestations of influenza A infection in adults. Otitis media (OM) is characterized by the presence of in-Experimental respiratory virus infection of human adults has been used to study the pathogenesis of the virus infection and flammation within the middle ear and is second in frequency of diseases affecting infants and children only to upper respiraits complications. In two studies, experimental influenza A virus infection caused sequential otologic complications, intory tract infections (URIs) [1]. Established OM is refractory to current methods of medical treatment and can persist for cluding eustachian tube dysfunction (80%), middle ear underpressures (70%), and OM (20%) after the initial expression of weeks, months, or even years [2]. Epidemiologic studies show that ú50% of new episodes of OM are temporally associated the signs and symptoms of the primary infection [7,8]. These observations suggest a causal pathway leading from virus infecwith a viral URI, and experimental studies document a causal relationship between the two diseases [3 -8]. Our understandtion to OM via the intermediate development of eustachian tube dysfunction and middle ear underpressures. This experimental ing of OM pathogenesis predicts a temporal delay between the onset of virus infection, symptom presentation, and OM. In setting may be ideal for evaluating strategies to prevent the otologic complications of a viral URI, since objective markers theory, this delay can be exploited to reduce the risk of otologic complications by treating the primary virus infection. This of otologic involvement are provoked in relatively high number, there appears to be a window for prophylaxis of the complistrategy has advantages over the prolonged use of antivirals for prophylaxis. Since the target population is circumscribed cation by antiviral treatment after symptom presentation, and an approved relatively safe and effective antiviral, rimantadine, to symptomatic ''at risk'' persons, the required duration of therapy can be limited to the expected period of viral shedding, is available for treatment [9 -11]. The aim of the present stu...

Insights into the Interaction between Influenza Virus and Pneumococcus

“…Analyses of multiple trials studying treatment of influenza with NA inhibitors concluded that lower respiratory tract complications, antibiotic use, and hospitalizations could be prevented both in healthy adults under 65 years old and in those who were 65 years or older or had chronic illnesses (29,76). Similar effects on secondary complications such as bacterial pneumonia have not been seen with the M2 inhibitors amantadine and rimantadine (36,110).…”

Influenza virus inhibits amiloride-sensitive Na+channels in respiratory epithelia

“…1e) is 10-to 1,000-fold lower than the viral concentrations measured in the nasal turbinates and lungs of mice infected for 3-4 days with influenza (38)(39)(40)(41) and the role of these channels in controlling the amount of fluid in the respiratory tract (4,42), the present findings provide an explanation for the accumulation of fluid in the respiratory tract that is a feature of influenza infections (11,(13)(14)(15)(16). The role of epithelial Na ϩ channels in maintaining the middle ear cavities free of fluid (43,44) suggests that downregulation of Na ϩ channel activity may also underlie the known association between influenza infections and otitis media (11,45). Finally, our observation that influenza hemagglutinin inhibits Na ϩ channel activity may point the way to the development of a novel alternative to the use of Na ϩ channel blockers such as amiloride in the treatment of the Na ϩ channel overactivity seen in cystic fibrosis (46).…”

Influenza Infection in Patients Before and After Liver Transplantation

“…They appear to shorten the duration of influenza symptoms when administered in the first 48 hours of infection, although the incidence of complications does not seem to be affected. 85 Rimantadine appears to be better tolerated and carries less central nervous system side effects 86 ; its pharmacokinetics are not altered in patients with chronic liver disease. 87 Rare adverse reactions include tremors, insomnia, dizziness, excitability, ataxia, and psychosis; gastrointestinal intolerance is more common.…”